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Quik 510k Pilot – Explanation of Quik 510k Pilot

There are 38 product classification codes that the FDA selected for the Quik 510k Pilot program to evaluate version 3 of the eSubmitter software.

510k Quik Pilot Product Codes 1 Quik 510k Pilot   Explanation of Quik 510k Pilot

What are the three (3) advantages of the new Quik 510k pilot program?

There are three (3) advantages of using the eSubmitter software as part of the Quik 510k pilot.  The first advantage of using the eSubmitter software is that the refusal to accept (RTA) process will be eliminated. This change is enormous because nearly 50% of submissions are rejected during the RTA screening process. The hope is that the eSubmitter software will prevent companies from submitting submissions that are missing required content, and therefore the RTA process will not be needed. However, we have seen many submissions placed on hold for technicalities rather than sub-standard submissions. Consequently, it will be fascinating to see the FDA reported outcomes from the Quik 510k pilot.

The second advantage of using the eSubmitter software is that the reviews will be interactive. This means that reviewers are not expected to have any additional information (AI) requests. This also means that submitters will need to respond to questions from reviewers quickly. For example, I have received a call on Friday afternoon after 5:00 pm EDT asking if I could revise to document and email that document to the reviewer by Monday morning. This is an extreme example, but 48-72 hours is typical for a required turn-around during interactive reviews.

The third advantage of using the eSubmitter software is that the FDA is targeting completion of their 510k review within 60 days. This 30-day reduction may seem huge, but the FDA already cut 15 days off its review timeline by eliminating the RTA screening. Second, the FDA picked 38 product classification codes that should not have difficulty reviewing in 60 days. Not all product classifications have the same amount of testing data required, and I do not expect the FDA to be able to review all product classification codes in 60 days–even with eSubmitter.

Although the Quik 510k pilot mentioned that submissions would be zipped, eSubmitter is also designed for electronic submissions through an electronic submissions gateway (ESG). An ESG has the added advantage that you will not need to ship your submission via FedEx. This advantage will gain you only a maximum of 24 hours, but I wish I had those 24 hours last week. Every year, in the last week of September, all the small businesses with small business qualifications try to submit their 510k before the end of the fiscal year (i.e., September 30). This year I had four clients that were in this position. One was unable to get the data they needed to complete their submission before September 30. The other three were making last-minute changes up until the afternoon of Thursday, September 27. One of those submissions was extremely challenging because the submission included video files that exceeded 1GB in total. Therefore, I called CDRH’s eCopy Program Coordinators at 240-402-3717. They were accommodating. They said that it would be best to provide two identical eCopies or to save the MISC FILES and STATISTICAL DATA folders on a separate flash drive. The reason for this is that very large submissions can take days to upload into the CDRH database. Therefore, the picture below shows you what my final solution was for the three submissions this week. The De Novo submission had to be split.

20180927 121031 Quik 510k Pilot   Explanation of Quik 510k Pilot

What our firm has done to take advantage of the Quik 510k pilot

If you have a product with any of the 38 product classification codes listed above, and you need to submit a 510k in the next six months, you are very fortunate. The FDA will prioritize your submission, and you are likely to be able to get your device cleared in 60 days or less. Our firm is very anxious to take part in this pilot because the FDA intends to require the eSubmitter software for all submissions in the future, and we expect other product classification codes to be added to the pilot over time. We process dozens of 510k submissions each year, and mastering the nuances of the software is critical to our continued success. I already downloaded the software and installed it onto my computer. I also created a complete submission as a test. eSubmitter saved several hours in the preparation of a 510(k) from the typical 40 hours the process takes. Therefore, I expect the implementation of new eSubmitter software to a triple win for the FDA, clients, and our firm. I plan to request that the FDA add De Novo submissions next to this pilot. The reason is that De Novo submissions typically have more content, and the content is more variable. I think this would be an extremely challenging test for eSubmitter, and the relatively small volume of De Novo submissions would limit the impact upon FDA resources.

Changes to eCopy Requirements in 2018

In 2017, the FDA indicated that eSubmitter software was going to be revised, and it would be approximately two years before companies would be able to submit a 510k electronically to the FDA. Until then, companies must ship an electronic eCopy and a paper copy to the FDA Document Control Center (DCC). The eCopy guidance states, “An eCopy is accompanied by a paper copy of the signed cover letter and the complete paper submission.” However, the FDA’s eCopy guidance has not been updated since December 3, 2015. There are some unofficial changes to the policy, and the FDA no longer requires the complete paper submission. Instead, you can submit an eCopy accompanied by a paper copy of the signed cover letter.

Before February 2018, we would print 1,000+ pages for each 510k submission, pack two 3” three-ring binders in 12”x12”x6” ULine boxes and ship the box to the FDA overnight via FedEx. We typically would charge $400 for this eCopy service. After the unofficial policy change, all of our 510k submissions consist of a paper copy of the cover letter and an eCopy on a USB flash drive. We only charge $150 for the FDA eCopy service, and 100% of our eCopy submissions have been uploaded without problems this year.

What is the difference between creating an eCopy and submitting it with eSubmitter (cited from FDA website)?

There are four differences between eSubmitter and eCopies:

  1. An eSubmission package contains PDF attachments and XML file types. The XML files are intended for CDRH IT systems to process the application. Reviewers will not see these XML files. 
  2. The parts of the eCopy guidance that describe the structure of a 510(k) submission will not apply to the Quik Review Program Pilot.
  3. An eSubmission is organized according to the layout of the template, which places administrative documents (e.g., Form 3674, the 510(k) Summary, the Truthful and Accurate statement) at the end of the submission because their applicability is determined based on the answers to questions in the body of the template (e.g., Form 3674 is only required if the applicant indicates clinical data are included).
  4. Electronic signatures are used in the submission (e.g., on the Truthful and Accurate statement), rather than physical signatures.

eSubmitter Template Options

For device 510k submissions, the FDA’s eSubmitter gives you three options:

  1. Template Version 1.3, for In Vitro Diagnostic 510k submissions to CDRH only, allows you to create a 510k submission and the eSubmitter software will package your submission in a specially formatted zip folder that you can save to a compact disc (CD), digital video disc (DVD) or flash drive. Then you must print a paper copy of your signed cover letter and ship the eCopy created by eSubmitter with your paper copy of the cover letter to the FDA DCC.
  2. Template Version 1.2.1, for Non-In Vitro Diagnostic 510k submissions that are among the 1,000+ other product classifications not included in the Quik 510k pilot (CDRH: Medical Device eCopies), you can create a 510k submission and the eSubmitter software will package your submission in a folder for you. You can then copy the contents of that folder to a compact disc (CD), digital video disc (DVD), or flash drive. Then you must print a paper copy of your signed cover letter and ship the eCopy created by eSubmitter with your paper copy of the cover letter to the FDA DCC.
  3. Template Version 3.2, for Non-In Vitro Diagnostic 510k submissions that are among the 38 product classification codes that are listed above for the Quik 510k pilot program. This allows you to create a 510k submission, and the eSubmitter software will package your submission in a specially formatted zip folder that you can save to a compact disc (CD), digital video disc (DVD), or flash drive. Then you must print a paper copy of your signed cover letter and ship the eCopy created by eSubmitter with your paper copy of the cover letter to the FDA DCC. This template is unique to the Quik 510k pilot program. There is a red bar that appears at the top of the screen:

“This template should only be used to construct a submission if you are submitting it as part of the Quick Review Pilot. All others may use the content of this template as a reference to aid in constructing an eCopy. If you are not part of the Quick Review Pilot, do not construct a submission with this template, it will be rejected.”

When you create your eCopy, then you will need to create a volume-based or non-volume based submission in accordance with the eCopy guidance. The volume folders and/or files are saved to a compact disc (CD), digital video disc (DVD), or flash drive. Then you must print a paper copy of your signed cover letter and ship the eCopy you created with your paper copy of the cover letter to the FDA DCC.

Warning Symbol Quik 510k Pilot   Explanation of Quik 510k PilotWarning: If you are using Windows 10, and you save your eCopy or eSubmitter zip folder on a flash drive, Windows 10 will automatically create a hidden system folder titled “System Information Volume.”  This folder is created as a security feature to enable you to recover accidentally deleted content. However, this folder results in an error when the FDA attempts to upload your submission automatically. Therefore, you must remove this hidden system folder. Instructions for this can be found on our website page about eCopy hidden system files.

Posted in: 510(k)

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Are 510k pre-sub meetings a waste of time?

This article reviews four of the top reasons for why other companies feel requesting 510k pre-sub meetings is a waste of time, but you can’t afford to.

Requesting 510k pre sub meeting is a waste of time 1024x448 Are 510k pre sub meetings a waste of time?

It only takes my team 8-10 hours to prepare a 510k pre-sub request. The FDA does not charge you a cent for requesting 510k pre-sub meetings, and a pre-sub should be part of every design plan. But most companies are resistant to requesting 510k pre-sub meetings. Here are the top 4 reasons why companies tell me they don’t need to request a meeting:

It’s too late for requesting 510k pre-sub meetings

If you are less than a week away from submitting a 510k, it is too late for requesting 510k pre-sub meetings. The FDA target for scheduling a 510k pre-sub meeting is 60-75 days from the date your request was submitted. That’s 10-11 weeks. Most companies tell me that they plan to submit a 510k within weeks or a couple of months, but most of the companies take several months, and frequently there is a delay that requires six months or more. For example, what if your device fails EMC testing, and you have to change the design and retest for both EMC and electrical safety? At best, you will have an 8-week delay. If you submit a request next week, and everything goes as you plan, you can always withdraw your request for the pre-sub. If you encounter a delay for any reason, suddenly, it’s not too late.

Our design is not finalized yet

I believe that waiting until your design is almost complete is the number one reason why companies wait too long to request 510k pre-sub meetings. If they wait too long, then the previous reason for not requesting a meeting takes over. The ideal time to submit a pre-sub request is 75 days before you approve your design outputs (i.e., design freeze). However, very few people are precise in their design planning and execution. You should try to target sometime after you approve your design inputs, but before you approve your design outputs. As long as you submit an update to your pre-sub request two weeks before the meeting, the FDA will accept it. Also, you can always schedule a date that is later than 75 days if you realize you requested the meeting too early.

We don’t want to be bound by what the FDA says in the 510k pre-sub meeting

510k pre-sub meetings are “non-binding.” That means that the FDA can change their mind, but it also means you don’t have to do everything the FDA says in a 510k pre-sub meeting. If you don’t ask a question about testing requirements, that doesn’t mean that the FDA does not have any testing requirements. The FDA knows what previous companies have submitted for testing better than you do, and they may be in the process of evaluating a draft special controls guidance. If you ask questions, you will have better insights into what the FDA expects. Understanding FDA expectations helps you write better rationales for testing or test avoidance. You also might learn about deadlines for the implementation of new testing requirements that you might be able to avoid. Finally, you can ask the FDA about possible testing options you are considering if the FDA denies your most optimistic testing plans.

There is already a guidance document for our device

Not all device classifications have a guidance document explaining what information should be submitted in a pre-market 510k submission. However, there almost one hundred Class II Special Controls Guidance Documents. Therefore, there is a good chance that the FDA published special controls as part of the regulation for your device or as a guidance document. As part of the special controls, the FDA defines what performance testing is required for your device. If you already know what testing is required, then the value in requesting 510k pre-sub meetings is diminished. But at least three other key benefits remain.

First, you can verify that the predicate you plan to use for comparative testing is not going to be a problem. Although the FDA can’t tell you which predicate to pick, the FDA can tell you if there is a problem with the predicate you have selected. This is especially important if the product is not currently registered and listed, because you may not know if the device was withdrawn from the market after it was cleared.

Second, not all testing standards are prescriptive. Many tests have testing options that require you to make a decision. Input from the FDA may be valuable in making choices between various performance testing options. Sometimes you even forgo testing and provide a rationale instead. FDA feedback on any rationale for not doing testing is critical to prevent delays and requests for additional information later.

Third, there are many different FDA representatives that participate in 510k pre-sub meetings. The lead reviewer will invite specialists and the branch chief to the meeting. Each of these specialists can answer questions during a pre-submission meeting that they are not able to answer during the actual review process. You also have the opportunity to get feedback from the branch chief–who has insight from all the previous devices that were cleared with your product classification. Your lead reviewer is not likely to be as experienced as the branch chief, and may only have been working at the FDA for months. Your request for the 510k pre-sub meeting will help an inexperienced lead reviewer as much as it will help your company.

Learning More about 510k Pre-sub Meetings

On Thursday, February 22, there will be a free webinar offered on the topic of 510k pre-sub meetings. We had 50 people register for the webinar on the first day it was announced, and we have already answered more than a dozen related questions. If you are planning to submit a 510k this year, this webinar will show you exactly how to prepare your request for a 510k pre-sub. You will even receive copies of all of our templates for free.Stop wasting time and register now Are 510k pre sub meetings a waste of time?

Posted in: 510(k)

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Biocompatibility testing questions answered in pre-submission requests

This article is a copy of my responses to someone that submitted biocompatibility testing questions in preparation for a 510k pre-submission webinar.

510k pre submission webinar February 22 for LinkedIn.jpg 1024x459 Biocompatibility testing questions answered in pre submission requests

Can you please answer the following questions related to biocompatibility for a 510k pre-submission meeting request?

This was the request by a person that registered for a 510k pre-submission webinar that was recorded in February 2018. The person asked some great questions that are very similar to other clients I work with. They also requested the biocompatibility testing questions in a way that did not divulge any confidential information–other than to indicate they live in Germany. Therefore, I am sharing my email response with you. Please register for this webinar and submit your questions. Questions are entered in an open text box, and you have room to ask multiple questions.

Biocompatibility testing question #1: Does the FDA now already ask for the AET (Analytical evaluation threshold) for chemical analyses?

This is exactly the type of biocompatibility testing questions you should be asking in a 510k pre-submission meeting. If you ask, “What biocompatibility testing is required for a 510k?” You will only receive a reference to the FDA guidance for biocompatibility. A better approach is to ask a biocompatibility testing lab to provide a Biological Evaluation Plan (BEP). Then you can submit your plan as part of the 510k pre-submission meeting request and include this question regarding the section of the BEP where you explain how you intend to perform chemical characterization of your device and how you intend to determine whether the materials represent risks related to sub-acute toxicity and sub-chronic toxicity endpoints.

Biocompatibility testing question #2: How can I avoid time-consuming genotoxicity studies for FDA?

Typically if you perform the “Big 3” (i.e., cytotoxicity, irritation, and sensitization), and then you perform chemical characterization, you are often able to prepare a Biological Evaluation Report to explain why there are no identified compounds in the chemical characterization that would warrant performing the genotoxicity studies. This is also often true for acute toxicity testing and sub-chronic toxicity testing. This often saves > $10K. To verify the FDA will accept this approach, you will typically provide a biological evaluation plan (BEP) as part of your pre-submission request. Your biocompatibility testing questions should specifically reference your BEP.

Question #3: And how can I face FDA with a cytotoxic wound dressing but which passed irritation, sensitization, genotox, and pyrogenicity tests?

I had a product that contained aluminum. Aluminum is cytotoxic to the cell line that is used in the cytotoxicity testing. However, aluminum does not have a high level of toxicity for the route of administration for that product. You should identify the reason why your product is cytotoxic and then explain why the device is no toxic for the intended use and duration of contact. This would normally be part of that BEP mentioned above.

Biocompatibility testing question #4: Which genotoxicity tests are state of the art for the FDA?

There are three ways to determine that. One is to look in the recognized standards database on the FDA website. The second is to review the FDA guidance on biocompatibility and application of ISO 10993-1. Finally, you can ask the FDA about the suitability of another test you want to perform during a pre-sub. If they prefer a different test, they will say so in an email response, and they are available for discussion by conference call during the pre-sub meeting to clarify their response.
I did not answer this question outright, because biocompatibility requirements change over time. This is also true for other verification testing standards. In fact, for one 510k project, I had seven different standards change just before submission. During a pre-submission meeting, the FDA should make you aware of coming changes to these tests. Also, better biocompatibility testing labs are aware of the changes before they are implemented. This is because the lab managers participate in the committees that revise and update international standards.

Will the meeting be recorded since I live in Germany?

Yes, all of my webinars are recorded. You will receive an email with a link for downloading the recording within 24 hours of completing the original live webinar or at the time of purchase if you are purchasing one of our previously recorded webinars. You can also schedule calls with me as a follow-up using the following link: http://calendly.com/13485cert/30min.

Posted in: 510(k)

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MDUFA IV – FDA User Fee Increase – Strategic Implications

This article identifies the strategic implications of the FDA user fee increases resulting from MDUFA IV starting in FY 2018.

FY 2018 MDUFA Fees MDUFA IV   FDA User Fee Increase   Strategic Implications

You didn’t know the FDA user fee increased?

In August, the FDA publishes the new FDA user fee schedule for the next fiscal year, which begins on October 1. Last year the FDA published an updated small business guidance document in early August that included the fee schedule. This year, the release of the FY 2018 FDA user fee schedule was delayed until the end of August, because the re-authorization of user fees was not approved until August 18, 2017.

The MDUFA IV user fee schedule was negotiated in October of 2016, and the new user fee schedule proposed to increase the user fees to $999.5 million. That negotiated plan called for an increase in standard fees for 510k submissions while keeping small business fees lower. The final enacted MDUFA IV user fees follow this plan. There is a significant difference between PMA fees and 510k fees in the new fee schedule. There was a 33% increase for all PMA-related standard and small business fees. However, standard 510k fees increased by 125%, while small business fees for a 510k increased by 13%. The establishment registration fees increased by 37%, and there is still no discounted registration fee for small businesses. Finally, the biggest change is there will now be a fee for De Novo applications.

Implications of the De Novo FDA user fee increase

Congress authorized the MDUFA III fees in 2012 for five years, and there were no fees associated with De Novo applications. In 2012, the Food and Drug Administration Safety and Innovation Act (FDASIA) also streamlined the De Novo application process. The purpose of having no fees, and for streamlining the process, was to encourage medical device innovation. However, only 40% of De Novo application reviews were completed within 150 days during 2015 and 2016. The balance of the applications required 200 to 600+ days to complete. Negotiations between the FDA and industry in 2016 resulted in an agreement to trade an increase in FDA user fees for a decrease in the review time required for 510k clearance. However, the FDA also committed to decreasing the De Novo application review time to less than 150 days as follows:

De Novo application decision goals for MDUFA IV 1024x118 MDUFA IV   FDA User Fee Increase   Strategic Implications
Unfortunately, the agreed FDA user fee for De Novo applications in MDUFA IV for FY 2018 is $93,229 as a standard fee and $23,307 for small businesses. During the past five years, during MDUFA III, companies that felt they had a potential De Novo application would try to persuade the FDA that a borderline 510k submission should be a De Novo application instead. However, under MDUFA IV, you will be more likely to persuade the FDA that a borderline classification should be considered for a 510k submission instead of a De Novo application.

Also, you should plan your De Novo application more carefully than you might have for a free application. Pre-submission meeting requests should always be submitted during the development process, and these pre-sub requests should be submitted at least 90 days before your design freeze. Special consideration should also be devoted to risk analysis and gathering preliminary data to demonstrate the effectiveness of the risk controls you select to ensure that the clinical benefits of your device outweigh the residual risks of the device after implementing risk controls. Ideally, you will gather enough evidence to create a draft special controls guidance document to submit to the FDA as a supplement to your pre-submission meeting.

If you are planning a De Novo application for FY 2018, you should expect your FDA reviewer to pay special attention to ensuring that there are no unnecessary delays in the review process. You should also monitor the FDA’s new final guidance webpage for the release of a final guidance document for De Novo applications. The draft guidance was released on August 14, 2014. Creating final guidance will probably be a priority for FY 2018.

Implications of the 510k FDA user fee increase

The standard FDA user fee for a 510k increased 125% from $4,690 to $10,566. However, the absolute dollar amount of a 510k submission is still less than the cost of biocompatibility testing or sterilization validation. Therefore, the increase should not significantly decrease the number of submissions. However, the small business fee has only been increased by 13%. Therefore, if you are a small business (i.e., income < $100 million), you should complete an application for small business qualification as soon as you can (i.e., October 1, 2017) to make sure that you are eligible for the discounted fee when you submit your next 510k submission. If you need help preparing your small business qualification form, there will be a webinar on this topic Friday, September 8, 2017.

When you are planning a 510k submission, you should also determine if your device product classification is eligible for third party review. In the past, the increased cost of the third party review made submission of a 510k to a third party reviewer unattractive. However, the fees for third-party reviews range from $9,000 to $12,000 typically. Therefore, there may be no difference in the fee for a third party review unless your company is a qualified small business.

Implications of MDUFA IV FDA user fee increase

The increase in the annual establishment registration fee is 37% for medical device firms to $4,624. If you are already registered as a medical device firm, you should increase your annual budget for the establishment registration fee accordingly. If you are about to launch a new product, remember that you are required to register and list your product within 30 days of distribution of your product. Therefore, if shipments are going to begin in September, you don’t need to register until October (i.e., after the start of the new fiscal year). Therefore, you may be able to avoid paying the FY 2017 establishment registration and only pay the FY 2018 establishment registration. This would not be the case for foreign firms that need to import the product prior to distribution.

What you can do about MDUFA IV fee increases now.

You may not be able to change the user fee schedule for FY 2018, but there are three things you can do now to improve your situation. First, if you are a small business, you can speak to your accounting department and get them to provide a copy of the FY 2016 tax return so that you can complete the small business qualification form on October 1. Second, you should contact Regulatory Technology Services and the Third Party Review Group to obtain a quote for a third-party review of your 510k submission instead of submitting directly to the FDA. Third, you should add a reminder to your calendar for August 1, 2018, to start reviewing the FDA website and other sources for an FY 2019 FDA user fee schedule.

Learning how to submit a small business qualification form

If you have not completed a small business qualification form before, you can learn how to prepare your application for small business qualification by registering for my webinar on Friday, September 8, 2017.

Posted in: 510(k), FDA

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Performance Qualification (PQ) for EO Sterilization Validation

The article explains requirements for a performance qualification (PQ) of EO sterilization validation and how it is different from other PQ process validations.

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Mind your ps and qs 1024x291 Performance Qualification (PQ) for EO Sterilization Validation

Performance Qualification (PQ) – What is the difference between an IQ, OQ, and PQ?

When you are performing a process validation, the acronyms IQ, OQ, and PQ sometimes confuse. IQ is the installation qualification of the equipment used in your validated process. The purpose of the installation qualification is to make sure that your equipment was installed correctly–this includes calibration and connection to utilities. OQ is the operational qualification. The purpose of the operational qualification is to make sure that the equipment you are using is capable of operating over the range of parameters that you specify to make your product. The PQ is a performance qualification. The purpose of the performance qualification is to ensure that you can consistently make a product within specifications (i.e., repeatable).

Different Definitions for Operational Qualification (OQ)

The GHTF guidance document for process validation provides the following definition for an OQ: “Establishing by objective evidence process control limits and action levels which result in a product that meets all predetermined requirements.” ISO 11135-1:2014, the international standard for ethylene oxide (EO) sterilization validation, provides a slightly different definition for an OQ: “process of obtaining and documenting evidence that installed equipment operates within predetermined limits when used in accordance with its operational procedures.” The difference in these two definitions is essential because the OQ is typically performed by contract sterilizers and does not need to be repeated unless there is a significant change or maintenance to the sterilizer that requires repeating the OQ. In contrast, when you perform an OQ for packaging, the OQ is specific to the packaging materials you are going to be sealing. Therefore a new OQ is required whenever new packaging materials are developed. For EO sterilization, the analogous step of the validation process is called a microbial performance qualification (MPQ).

Performance Qualification (PQ) = MPQ + PPQ

A performance qualification (PQ) for ethylene oxide sterilization validation consists of two parts: 1) microbial performance qualification (MPQ), and 2) physical performance qualification (PPQ). The microbial performance qualification is intended to determine the minimum process parameters for the EO sterilizer sufficient to ensure product bioburden is killed. These parameters are referred to as the half-cycle because the full production cycle will be twice as long in duration. For example, a half-cycle consisting of 3 injections will correspond to an entire cycle of 6 injections.

What are fractional cycles?

Fractional cycles are typically shorter in duration than the duration of a half-cycle. The purpose of a fractional cycle is to demonstrate that external biological indicators (BIs) located outside of your product, but inside the sterilization load, are more challenging to kill than internal BIs. Fractional cycles are also be used to demonstrate that the product bioburden is less resistant than the internal BIs. To achieve both of these objectives, it is typical to perform two fractional cycles at different conditions to make 100% kill of internal BIs and partial external BI kill in one fractional cycle, and 100% kill of product bioburden but only partial kill of internal BIs in the other fractional cycle. When your goal is partial kill, you should also target more than one positive BI, because this reduces the likelihood that poor technique resulted in a BI positive from growth.

Microbial Performance Qualification (MPQ)

The microbial performance qualification (MPQ) typically consists of three half-cycles and one or more fractional cycles. 100% kill of external BIs is not required for the MPQ during a half-cycle–only the internal BIs must be 100% killed, but the external BIs are only useful if 100% kill of the external BIs is achieved in the full cycles. If you are re-validating the sterilization process, you are only required to complete one-half cycle and one fractional cycle. For re-validation, the fractional cycle is intended to achieve a 100% kill of product bioburden. Still, only partial kill of internal BIs to verify that the product bioburden remains less resistant to sterilization than the internal BIs. You are also required to perform bioburden measurements of non-sterile products for the initial MPQ and re-validation to demonstrate that bioburden can be adequately recovered from the product and measured.

Physical Performance Qualification (PPQ)

The physical performance qualification (PPQ) typically consists of three full cycles and measurement of EO residuals in accordance with ISO 10993-7:2008. If PPQ is performed during the MPQ, then it is only necessary to complete one full cycle–assuming the MPQ consists of at least three half-cycles. If you are performing a re-validation of the sterilization process, then you are required to complete three full cycles and measurement of EO residuals.

Repeatability, Reproducibility, Product Variability and Environmental Factors

Typically a performance qualification (PQ) is intended to verify that the same person can repeat the process multiple times, other people can reproduce the first person’s results and any variation product from lot to lot will not prevent the process from producing an acceptable product. Besides, any variation in environmental factors should be assessed during a PQ. In sterilization processes, however, the equipment is typically automated. Therefore, variation between operators is usually a non-issue. Also, sterilization lots typically consist of a large volume of products where multiple samples are tested for sterility. Therefore, performing three runs sufficiently challenges the repeatability and reproducibility of the sterilization process–including any product variability. The issue of environmental variations in heat and humidity is addressed by designing preconditioning cycles into the sterilization process. Sensors are included in each validation load to verify that the process specifications were achieved and maintained for temperature and humidity. Still, the sensors also help to identify the worst-case locations in a load to use for sampling and placement of BIs.

If you are interested in learning more about sterilization validation, please read our blog from last year on an evaluation of the need to re-validate your sterilization process, or you can watch our webinar on sterilization and shelf-life testing. You can also purchase our procedure for EO sterilization validation by clicking on the link below.

Purchase the EO Sterilization Validation Procedure (SYS-031) – $299

EO Sterilization Cycle 1 150x150 Performance Qualification (PQ) for EO Sterilization Validation
SYS-031 EO Sterilization Validation Procedure

This new procedure defines the requirements for ethylene oxide (EO) sterilization validation and revalidation which has been outsourced to a contract sterilizer.

Price: $299.00

 

Posted in: Process Validation, Validation

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Safety Agency Mark – Is it required for medical electrical equipment?

This article explains when a safety agency mark is required for electrical medical equipment for products sold in the USA.

Safety Marks 1024x228 Safety Agency Mark – Is it required for medical electrical equipment?

What is a safety agency mark?

Examples of a safety agency mark include UL, CSA, Intertek, SGS Q-mark, and other marks indicating that a recognized testing lab completed the electrical safety testing, and the device passed the testing. Health Canada requires a safety agency mark to certify approval by a lab that is accredited by the Standards Council of Canada (SCC). However, device manufacturers are frequently unclear what the requirements are in the USA for electrical medical equipment regarding a safety agency mark.

Leo Eisner’s explanation of the requirements for a safety agency mark in the USA

Leo Eisner of Eisner Safety was kind enough to answer this question. The simple answer is yes. In the US, there is a requirement for equipment in the workplace to have an NRTL Safety Agency Approval Mark for the applicable category on the device to meet OSHA requirements. The requirements for NRTL approval of electric equipment (or medical electrical equipment) are in 29 CFR 1910.303(a) and 29 CFR 1910.307(c). Because of these requirements, most electric equipment used in the workplace must be NRTL approved. Biomeds maintain and track all the medical equipment in hospitals and clinical environments, and the biomeds usually insist upon an Agency Approval Mark. However, the biomeds may not be aware of the NRTL requirements.

What is an NRTL?

An NRTL is a Nationally Recognized Test Lab that is approved or authorized by Occupational Safety & Hazard Administration (OSHA) for specific device test standards (i.e., UL 60601-1 [National deviation version of IEC 60601-1, 2nd ed. medical electrical equipment standard] and / or AAMI ES 60601-1 [National deviation version of IEC 60601-1, ed 3.1], among many other standards) to allow a US Mark to be placed on approved devices that meet the applicable standard. Not all NRTL labs can test to the listed medical electrical standards for medical electrical equipment to allow a US mark to be placed on devices. You need to go to the OSHA NRTL site to verify that the test lab can issue a US mark. Within the lab’s link, you can find which standards each test lab is allowed to issue US Marks for.

Posted in: IEC 60601

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IFU validation is not a risk reduction – Deviation 7

This article describes how to perform IFU validation before commercialization and how to conduct post-market surveillance to ensure that your IFU continues to be suitable as your user population and patient population expand.

IFU Validation and PMS IFU validation is not a risk reduction   Deviation 7

Most companies create an IFU for a new product by plagiarism. They merely copy a competitor’s IFU and change the name. If a regulatory expert creates the IFU, the IFU will be nearly identical to the competitor IFU. However, if a marketing person creates the IFU, the IFU will explain how your product is different from the competitor product. Neither approach is practical.

Creating a risk-based IFU

EN ISO 14971:2012 identifies deviations between the ISO 14971:2007 international standard and the three EU Directives. However, deviation #7 is specific to labeling and instructions for use. Even if your product is not CE marked, you should be developing a risk-based approach to IFUs. The priority of risk controls is to eliminate and reduce risks by design, manufacture, and selection of materials. The second priority is to implement protective measures such as alarms to warn users of risks. The last priority for risk controls is to inform users of residual risks. The best practice is to utilize a risk traceability matrix to document each of the risk controls you implemented to eliminate and reduce the risks of hazards identified.

The EN version of ISO 14971 will not allow you to reduce risks quantitatively in your risk assessment for information provided to users about risks, because this type of risk control is not entirely effective. However, you are required to verify that each residual risk is disclosed to users in your IFU, and you must validate that your warnings, precautions, and contraindications are adequately identified such that users understand the residual risks. You are also required to determine any user training needed to ensure specified performance and safe use of your medical device in accordance with ISO 13485:2016, Clause 7.2.1d. Clause 7.2.2d) requires that your company ensure that user training is made available. Any user training you provide should also be validated for effectiveness.

When to perform IFU validation

Some companies ask physicians that helped them with product development review draft IFUs. However, these physicians are already familiar with your product, your company, and they are highly skilled in the specific procedures your device will be used for. After your experts have made their final edits to your draft IFU, you now need a “fresh set of eyes.” The best approach is to validate the effectiveness of your IFU with potential users that don’t know you or your company. If your product requires animal performance testing or human clinical studies, you could use these studies to validate your IFU. However, I recommend conducting a simulated use study before conducting animal or human studies. Conducting a simulated use study before animal and human studies can prevent deviations from your documented protocols that were caused by the inadequate review of the IFUs.

Methods of IFU validation

The best method for validating your IFU is to perform a simulated use study or human factors study. The FDA published a human factors guidance document that can help you assess the risk of human factors and ergonomics. The FDA guidance requires that you identify your intended user population(s). For each individual population of users, you are required to have a minimum of 15 users for your study. If your product is not for specific indications, you may be able to select 15 users at a few sites randomly. However, if your device is intended for two different specialties, then you need to 30 users–15 for each specialization.  I recommend recording a video of simulated use studies too. Videos identify small details that you might miss, and clips from the videos are useful in creating training videos for future users.

Gathering Post-Market Surveillance

Post-market surveillance is not just asking customers if they are satisfied. You need to continue to monitor adverse event databases, your complaint database, and any service records to determine if there are any new risks and to verify that the risks you identified were accurately estimated concerning severity and probability of occurrence of harm. Clinical studies and PMS are the only way you can gather data regarding the likelihood of occurrence of harm. When you design your post-market surveillance questions, make sure you include questions explicitly targeting the residual risks you identify in your IFU. You should also ask, “What indications do you use this device for. Specifically, please identify the intended diagnosis, treatment, and patient populations.” This wording is more effective than asking if a physician is using your product “off label.”

Revalidation of IFU after labeling changes

Changes to labeling and IFUs should always be considered design changes and may require revalidation. If the switch is in response to a complaint or CAPA, then you must revalidate the IFU and labeling to verify the effectiveness of your corrective action. Any validation should be documented, reviewed, and approved before implementation, and acceptance criteria should be determined ahead of time. Your acceptance criteria should be quantitative, so you can objectively determine if the change is valid or not. You might be able to copy your previous IFU validation protocol or simulated use protocol and simply repeat the validation precisely as you did before with new users. However, sometimes the reason why the IFU was not 100% effective in the past is that the risk you are addressing in the revised IFU was not evaluated adequately in the original simulated use protocol.

New webinar for risk-based IFU validation and PMS

If you want to learn more about using a risk-based approach to developing IFUs, validating IFUs, and performing post-market surveillance to monitor the effectiveness of your IFU, then please click on the webinar link below.

IFU Validation Webinar Button 300x62 IFU validation is not a risk reduction   Deviation 7

If you are interested in ISO 14971 training, we were conducting a risk management training webinar on October 19, 2018.

Posted in: Clinical Studies & Post-Market Surveillance, Validation

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DHF Required for a Class I Device? At least 67%…

Is a DHF required appears to be a simple yes/no question? If you reword the question, however, you get a very different answer.

Is a DHF required DHF Required for a Class I Device? At least 67%...

If you ask, “how much less documentation is required for the design of a Class 1 device compared with a Class 2 device?” you get a very different answer. Instead of 0% (Yes, a DHF is required) of 100% (No DHF required), the answer is that you need 33% less documentation for the design of a Class 1 device.

The FDA shared a presentation on design controls in 2015.

In that presentation, the agency identified six Class 1 product classifications that require design controls, while thousands of Class 1 product classifications do not need design controls. Despite the lack of design controls, manufacturers must still maintain a procedure for design transfer, maintain an approved device master file with all the approved design specifications (i.e., design outputs), and design changes may still require revalidation before implementation.

Why is a DHF Required for Class 2, but Not for Class 1?

Class 1 devices are simple devices that are already on the market and have a history of clinical safety. Class 2 devices are generally more complex and present a moderate risk. Therefore, changes in the technological characteristics often present a higher risk for Class 2 devices. When you design a Class 1 device, you still have to determine what your design specifications will be. Again, you don’t need: 1) to review and approve design inputs, 2) a procedure to document your design process, 3) to document formal design reviews, and 4) to create a design plan.

In the 1997 guidance document for design controls, the FDA states that a design transfer procedure should include at least three basic elements:

  1. design and development procedures should consist of a qualitative assessment of the completeness and adequacy of the production specifications;
  2. procedures should ensure that all documents and articles which constitute the production specifications are reviewed and approved; and
  3. procedures should ensure that only approved specifications are used to manufacture production devices.

The first of these basic elements is not required for Class 1 devices because product specifications for most Class 1 devices are simple. The other two requirements are fundamental principles of document control and configuration management. Therefore, you still need a design transfer procedure for Class 1 devices, but you don’t need to include the first element that relies upon design and development procedures.

If you have a Class 1 device, you must still comply with labeling requirements (i.e., 21 CFR 820.120). If your device is sterile, you must still validate and re-validate the process in accordance with 21 CFR 820.75. Class 1 products also require a device master record (DMR) in accordance with 21 CFR 820.181.

What is Not DHF required?

Needed for Class I (67%)

  1. Approved Design Outputs
  2. Labeling Procedure
  3. Approved Labeling
  4. Sterilization Validation Procedure
  5. Sterilization Validation Protocol and Report
  6. Design Transfer Procedure
  7. Approved DMR
  8. Design Change Procedure

Needed for Class II and Class I requiring Design Controls (100%)

  1. Design Control Procedure
  2. Design Plan
  3. Approved Design Inputs
  4. Approved Design Outputs
  5. Labeling Procedure
  6. Approved Labeling
  7. Sterilization Validation Procedure
  8. Sterilization Validation Protocol and Report
  9. Design Transfer Procedure
  10. Evidence of at least 1 Design Review
  11. Approved DMR
  12. Design Change Procedure

Therefore, although you do not technically have to have a DHF for a Class 1 products, the difference between the two categories is the following elements:

  1. Design Control Procedure
  2. Design Plan
  3. Approved Design Inputs
  4. Evidence of at least 1 Design Review

When an FDA inspection occurs, the investigator will review your design control procedure and then audit your DHF in accordance with your design plan.

When you have a Class 1 device, you are not typically inspected unless there is a problem. When ORA inspectors perform an inspection for Class 1 devices, the inspector looks for evidence of items in the first list.

If you are interested in learning more about design history files (DHF), please check out our DHF webinar.

Posted in: Design Control

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Checking adverse event history for your device and competitors

The article explains checking adverse event data for medical devices as part of design and development, risk management, and post-market surveillance.

TPLC Database Checking adverse event history for your device and competitors

When should you be checking adverse event history?

There are three times when you should be checking adverse event history:

  1. when you are planning a new or improved medical device, and you want to know how current devices on the market malfunction (design and development planning),
  2. when you are identifying hazards associated with a medical device as part of your risk management process, and
  3. when you are gathering post-market surveillance data about your device and competitor devices.

Where should you be checking adverse event history?

Most countries have some kind of database for gathering adverse event data for medical devices, but most of these databases are not open to the public. The most common question I am asked is, “How do you access the Eudamed database?” for reporting of adverse events in Europe. Unfortunately, you can’t access Eudamed. The Eudamed database is only available to competent authorities at this time. The primary publicly accessible database for adverse event reporting is the US FDA MAUDE database. The MAUDE database is also integrated with other FDA databases for 510k submissions and recalls. This combined database is called the Total Product Life Cycle database.

Are there other public databases for checking adverse event history?

Yes. The Therapeutic Good Administration (TGA) in Australia makes adverse event data publicly available. The TGA also has a national registry for implanted orthopedic devices that publishes an annual report. Other countries also have public registries.

When will checking adverse event data for Europe be possible?

The Eudamed database for Europe was created in 1999 by the German organization DIMDI. In 2000 the responsibility for the database was taken over by the European Commission. The latest update is that manufacturers will be responsible for updating the Eudamed database in the future as part of the new European Regulations. This requirement will be implemented during the next years. The database will also become accessible to the public.

When you collect post-market surveillance data, which data should you collect?

Searching for post-market surveillance data should be performed on a risk-based frequency. If you have a brand new device, a high-risk device, or a device that is implanted, post-market surveillance data should be reviewed frequently–either monthly or quarterly. The new European guidance document for clinical evaluation reports (MEDDEV 2.7/1 rev 4) requires that clinical evaluation reports be updated at least annually for these devices. It is also important that you collect post-market surveillance data for both your device and competitor products. Therefore, you should be reviewing all the publicly available adverse event databases. You should also be reviewing your complaint data, and you should be searching for journal articles that may include adverse event data–possibly associated with a clinical study.

Available Resources

If you want to learn more about post-market surveillance data collection, please visit our webinar page. There is also a procedure for Post-Market Surveillance (SYS-019).

Posted in: ISO 14971:2019 (Risk Management)

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Updating Training Procedure for Compliance with ISO 13485:2016

This article explains my process for updating training procedure SYS-004 for compliance with ISO 13845:2016 while the procedure was also simplified.

Training and Competency 1 Updating Training Procedure for Compliance with ISO 13485:2016

In addition to weekly blogging for the Medical Device Academy website, I am also updating each of my procedures for ISO 13485:2016 compliance. This week the training procedure (SYS-004) was updated. You are updating your procedures for compliance with the revised standard, but are you making any other strategic changes at the same time?

Changes to Training in ISO 13485:2016

The primary change to Clause 6.2 in ISO 13485 was the addition of the phrase, “shall document the process(es) for establishing competence, providing training, and ensuring awareness.” This doesn’t represent a change in the intent of the standard. Still, it does signal that certification bodies should be emphasizing the importance of assessing the effectiveness of training and competency–not just verifying the existence of training records.

Updating Training Procedure

The original version of SYS-004 had eight pages and included three different flow charts to explain the process. The procedure also required the use of a training plan for each employee. While I agree that managers should plan training if you make this a formal requirement with a controlled form, it creates an unnecessary burden for managers.

Therefore, when the procedure was updated to the requirements of ISO 13485:2016, the procedure was also simplified for smoother implementation by start-up companies. When you upgrade your procedures, you might look for similar opportunities to simplify and streamline the processes.

The updated procedure now has suggestions for how to consolidate specific roles for smaller companies. The procedure still references a training record for documenting training, but now there is also a reference to a training matrix to help document training requirements for each employee.

The FDA also requires that there are documented training requirements. Therefore, the procedure identifies the need to create a job description that includes training and competency requirements. The procedure does not, however, require that the job descriptions be maintained as controlled documents. If your company has multiple people with the same job function (e.g., customer service), then it might make sense to have a controlled document that is a job description for customer service. A company with four employees does not need controlled documents, and instead, a unique record for each employee makes more sense.

Updating Training Procedure to Explain How to Complete Forms?

Another option is to make your procedure very detailed to explain how to complete each section of a form, such as the training record (FRM-002) or the training matrix (FRM-026). However, I see very few managers struggle with completing training records. Therefore, instead, I plan to record a brief training webinar that explains how to fill in the forms. This will be provided as a free update to anyone that purchases the training competency procedure. This makes it easier to review the procedure for regulatory compliance and puts the details on how to complete forms in the training curriculum where it belongs.

If you have questions about how to update any of your procedures to ISO 13485, please email me at rob@13485cert.com. Maybe I’ll use your question as a topic for a future blog.

Posted in: ISO 13485:2016, ISO Certification

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